Our objective is to gain insights into the functions of polymorphonuclear leukocytes (PMNs) in human periodontal diseases. PMNs probably represent an important antibacterial defense system in the gingival crevice as well as an effector mechanism of inflammatory tissue injury. Our recent work has shown that Actinobacillus actinomycetemcomitans (AA) possess a potent leukotoxin(s) which kills human PMNs and monocytes. This and other evidence suggests that AA may be of pathogenic significance in the development of juvenile periodontitis. We propose a comprehensive microbiological, immunological and leukocyte functional study to define the interrelationships between AA infection of the gingival crevice, leukotoxin production and the immune response in subject with juvenile periodontitis and members of their immediate family. This information should help to clarify the role of AA in this poorly understood disorder. Another study will be initiated to examine the modulation of PMN function by saliva. Preliminary data shows that PMNs respond more aggressively (i.e., lysosome release) to saliva-coated as opposed to untreated oral bacteria. We will construct a model system using oral streptococci to monitor variations in the capacity of saliva to influence PMN function and to delineate the specific salivary proteins and mechanisms involved. The results are pertinent to the pathogenesis of cervical dental caries and marginal periodontitis. Lastly, we propose an expansion of on-going research on the capacity of PMNs to influence mononuclear cell immune function. We will focus upon the role of PMN lactoferrin as a modulant of in vitro antibody synthesis, monokine and lymphokine production, blastogenesis, phagocytosis, etc. These results will help to define the potential mechanisms of cell-cell interactions in inflammatory lesions, such as periodontal disease.